| The liver is an important detoxification organ in human body.With the accelerated pace of life and serious environmental pollution,the load of the liver has been increased gradually.Generally,the liver injury is caused due to the stimulation of alcohol,drugs,viruses,as well as toxins coming from intestinal tract.Therefore,prevention and treatment of liver injury will become the new hotspot.Currently,the mechanism of liver injury is unclear,and there is no drug to effectively prevent and treat liver injury.However,a large number of studies have shown that some probiotics can prevent and treat liver injury.In this study,we build acute and chronic liver damge models using mice to evaluate the hepatoprotective effect of Lactobacillus plantarum C88 and explore its mechanism.In this study,we established acute liver injury model induced by LPS(Lipopolysaccharide,LPS)/D-galactosamine(2-amino-2-deoxy-D-galactose,D-GaLN)using male ICR mice to explore the protection of L.plantarum C88 to acute liver injury.The general signs,organ index,serum antioxidant enzyme activity,serum inflammatory cytokines content were detected and the pathological changes of liver were observed so as to evaluate the antagonistic effect of L.plantarum C88 to acute liver injury.Moreover,we used real-time PCR and Western blot to study the effects of L.plantarum C88 on nuclear factor-erythroid-related factor 2(Nrf2),Nuclear factor kappa-light-chain-enhancer of activated B cells(NF-?B)expression,as well as intestinal barrier.The results showed that compared with the model group,L.plantarum C88 could reduce the contents of alanine transaminase(ALT),aspartate aminotransferase(AST),Tumor Necrosis factor-?(TNF-?),interleukin 6(IL-6),interleukin 12(IL-12)and lipoperoxides(LPO)in the serum of LPS/D-GaLN induced liver injury mice,and increase the activity of superoxide dismutase(SOD).In addition,compared with the model group,L.plantarum C88 reduced the activity of CYP2E1,RelA/P65 nuclear import quantity,while increasing Nrf2 nuclear import quantity and reducing P38 phosphorylation level.Compared with the model group,L.plantarum C88 reduced the level of hypoxia inducible factor-1?(Hif1?)in intestine and improved the tight junction protein and blocking protein contents,indicating that the protective effect of L.plantarum C88 to LPS/D-GaLN induced liver injury may be associated with the inhibition of NF-?B nuclear import quantity,promotion of Nrf2 protein nuclear import to activate ARE,inhibition of Hif1? expression level and enhancement of intestinal barrier,which ultimately improved anti-oxidation and anti-inflammatory ability of the body.To evaluate the protective effect of L.plantarum C88 on alcohol-induced chronic liver injury,in this study,the male ICR mice were used to establish alcoholic liver injury model,and the general signs,organ index,serum or liver tissue antioxidant enzymes activity and vitality,serum inflammatory cytokines content were measured and the liver pathological changes were observed so as to evaluate the antagonistic effect of L.plantarum C88 on alcoholic liver injury.Moreover,it used real-time PCR and Western blot to detect the impact of L.plantarum C88 on Nrf2 and NF-?B(RelA / P65)expression to explore the molecular mechanism involved in antagonistic role to alcoholic liver injury.The results showed that compared with the model group,L.plantarum C88 could reduce level of ALT,AST,TNF-?,IL-6,Interferon-?(IFN-?)in serum of alcohol-induced liver injury and malondialdehyde(MDA)content in liver tissue,while improving SOD activity in liver tissue.Compared with the model group,L.plantarum C88 down-regulated the expression of RelA/P65,up-regulated the expression of Nrf2 and decreased P38(p-P38)phosphorylation level.In addition,compared with the model group,L.plantarum C88 decreased CYP2E1 level and improved intestinal tight junction protein and blocking protein contents,while down-regulating Hif1?,indicating that the protective effect of L.plantarum C88 to alcohol-induced liver injury may be associated with the inhibition of NF-?B expression and promotion of Nrf2 expression,which finally improved anti-oxidation and anti-inflammatory ability of the body and maintained the stability of intestinal barrier. |
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